7F8U

Crystal structure of the cholecystokinin receptor CCKAR in complex with lintitript

7F8U の概要

• エントリーDOI: 10.2210/pdb7f8u/pdb
• 分子名称: Fusion protein of Cholecystokinin receptor type A and Endolysin, 2-[2-[[4-(2-chlorophenyl)-1,3-thiazol-2-yl]carbamoyl]indol-1-yl]ethanoic acid (2 entities in total)
• 機能のキーワード: g protein-coulped receptor, cholecystokinin receptor cckar, lintitript, structural protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60862.23

構造登録者

Zhang, X.,He, C.,Wang, M.,Zhou, Q.,Yang, D.,Zhu, Y.,Wu, B.,Zhao, Q. (登録日: 2021-07-02, 公開日: 2021-10-13, 最終更新日: 2024-11-06)

主引用文献

Zhang, X.,He, C.,Wang, M.,Zhou, Q.,Yang, D.,Zhu, Y.,Feng, W.,Zhang, H.,Dai, A.,Chu, X.,Wang, J.,Yang, Z.,Jiang, Y.,Sensfuss, U.,Tan, Q.,Han, S.,Reedtz-Runge, S.,Xu, H.E.,Zhao, S.,Wang, M.W.,Wu, B.,Zhao, Q.
Structures of the human cholecystokinin receptors bound to agonists and antagonists.
Nat.Chem.Biol., 17:1230-1237, 2021

PubMed Abstract: Cholecystokinin receptors, CCKR and CCKR, are important neurointestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here, we report three crystal structures of the human CCKR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKR-gastrin in complex with G and G, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.

PubMed: 34556863
DOI: 10.1038/s41589-021-00866-8

実験手法

X-RAY DIFFRACTION (2.8 Å)